B. A. Moser, X. Cui, C. Loghin, A. Chaudhary, A. de la Peña, J. Y. Chien; Eli Lilly and Company, Indianapolis, IN
BACKGROUND: Dulaglutide is a long-acting, glucagon-like peptide 1 receptor agonist administered once weekly, by subcutaneous (SC) injection for the treatment of type 2 diabetes. The pharmacokinetics (PK) of a single dulaglutide 1.5 mg dose after SC injection into the arm and thigh, versus the abdominal wall, were assessed over a wide range of body composition and BMI.
METHODS: Healthy subjects (N=45) were randomly assigned to receive 3 single 1.5 mg SC doses of dulaglutide (1 per period) into the arm, thigh, and abdomen in an open-label, 3-period, randomized crossover study (BMI 19.4 - 44.7 kg/m2). PK analyses used non-compartmental methods and population PK modeling. Body composition using DEXA was correlated to PK.
RESULTS: Site of administration had no statistically significant effect on dulaglutide PK. Mean (90% CI) ratios of area under the plasma concentration vs. time curve were 0.973 (0.941, 1.01) for the arm and 0.989 (0.956, 1.02) for the thigh. Ratios of mean peak plasma concentration (90% CI) were 0.984 (0.925, 1.05) for the arm and 0.890 (0.838, 0.944) for the thigh. Median time of maximum concentration (48 hours) and mean half-life (4.3 days) were similar across sites. Body weight, BMI, tissue fat mass, and waist circumference were highly correlated, significant covariates on PK. The incidence of adverse events was generally similar across all injection sites for all subjects.
CONCLUSION: Injection site did not affect dulaglutide exposure; dulaglutide may be administered in the abdomen, upper arm, or thigh without dose adjustment over a wide range of BMI. Despite the significant correlations between measures, there was no clinically relevant body composition or size effect on dulaglutide PK. Thus, no dose adjustment is necessary based on any of these measures.